High levels of the hormone angiotensin II in the blood are associated with severe symptoms and subsequent outcome in patients with bird flu, reports two papers published in Nature Communications. The studies show that pharmacological reduction of angiotensin II levels alleviates disease symptoms in mice. These findings may, therefore, provide a biomarker and potential treatment strategy to address future flu pandemics.
Lanjuan Li, Chengyu Jiang and colleagues report that patients infected with H7N9 avian influenza have higher plasma levels of angiotensin II than healthy subjects or people suffering from swine flu. In the case of H7N9 patients, they find that angiotensin II concentration, viral load, disease progression and mortality are correlated, and that predictions of mortality based on angiotensin II are as good as, or better than, those based on other common clinical parameters, such as blood oxygen levels.
In a second study, Chengyu Jiang and colleagues show that angiotensin II levels are also elevated in individuals with H5N1 avian influenza, in comparison with healthy subjects. Moreover, they report that experimental infection of mice with H5N1 virus leads to increased angiotensin II levels and decreased expression of ACE2 (angiotensin-converting enzyme 2), a protein that inactivates angiotensin II. Finally, the team show that administration of human ACE2 ameliorates disease symptoms and reduces angiotensin II levels in H5N1-infected mice.
Taken together, these papers may have clinical implications and provide new insights into the mechanisms underlying disease progression in avian flu patients. However, further studies are needed to validate angiotensin II as a useful biomarker and to assess the potential therapeutic efficacy of ACE2.